ABSTRACT Intravenous thrombolysis and acute neurointerventional therapies such as or neurothrombectomy / aspiration should be compleed by two approaches in order to achieve meaningful success in acute stroke clinical practice

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doi: 10.5505/tbdhd.2020.41713

REVIEW DERLEME ACUTE STROKE NURSING: STANDARDS AND PRACTICAL APPLICATIONS

TURKISH CEREBROVASCULAR DISEASE SOCIETY AND THE SOCIETY OF NEUROLOGICAL NURSING JOINT STRATEGY PROJECT

Mehmet Akif TOPCUOGLU¹, Zeliha TULEK², Sakine BOYRAZ³, Atilla Ozcan OZDEMİR⁴, Aylin OZAKGUL², Ayşe GULER⁵, Bijen NAZLIEL⁶, Canan TOGAY ISIKAY⁷, Erdem YAKA⁸, Ethem Murat ARSAVA¹, Gülsen CAGLAR¹, Hadiye SIRIN⁵, Ipek MIDI⁹, Murat Mert ATMACA¹⁰, Naile ALANKAYA¹¹, Nedim ONGUN¹², Nurdan YILDIRIM¹³, Ozlem AYKAC⁴, Ozlem KUÇUKGUCLU¹⁴, Oznur USTA YESILBALKAN¹⁵, Recep BAYDEMIR¹⁶, Serefnur OZTURK¹⁷, Turkan ACAR¹⁸, Mukadder MOLLAOGLU^19,Ayfer KARADAKOVAN¹⁵, Zehra DURNA¹³

1Hacettepe University Faculty of Medicine, Department of Neurology, Ankara, TURKEY, ²Istanbul University, Cerrahpaşa Florence Nightingale Nursing Faculty, Istanbul, TURKEY, ³Adnan Menderes University, Faculty of Nursing, Department of Nursing, Aydin, TURKEY, ⁴Eskişehir Osmangazi University Faculty of Medicine, Department of Neurology, Eskisehir, TURKEY, ⁵Ege University Faculty of Medicine, Department of Neurology, Izmir, TURKEY, ⁶Gazi University Faculty of Medicine, Department of Neurology, Ankara, TURKEY, ⁷Ankara University Faculty of Medicine, Department of Neurology, Ankara, TURKEY, ⁹Dokuz Eylül University Faculty of Medicine, Department of Neurology, Izmir, TURKEY ⁹Marmara University Faculty of Medicine, Department of Neurology, Istanbul, TURKEY,

10Republic of Turkey Ministry of Health Sultan Abdülhamid Han Training and Research Hospital, Neurology Clinic, Istanbul, TURKEY, ¹¹Canakkale Onsekiz Mart University, Canakkale Helsth School, Department of Nursing, Division of Internal Medicine Nursing, Canakkale, TURKEY, ¹²Burdur State Hospital, Neurology Clinic, Burdur, TURKEY, ¹³Demiroglu Bilim University Florence Nightingale Hospital Nursing School, Istanbul, TURKEY, ¹⁴Dokuz Eylül University Faculty of Nursing, Department of Internal Medicine Nursing, Izmir, TURKEY, ¹⁵Ege University Faculty of Nursing, Izmir, TURKEY,

16Erciyes University Faculty of Medicine, Department of Neurology, Kayseri, TURKEY, ¹⁷Selçuk University Faculty of Medicine, Department of Neurology, Konya, TURKEY, ¹⁸Sakarya University Faculty of Medicine, Department of Neurology, Sakarya, TURKEY, ¹⁹Cumhuriyet University Faculty of Health Sciences, Değertment of Nursing, Division of Internal Medicine Nursing, Sivas, TURKEY.

ABSTRACT

Intravenous thrombolysis and acute neurointerventional therapies such as or neurothrombectomy / aspiration should be compleed by two approaches in order to achieve meaningful success in acute stroke clinical practice. The first is the “acute stroke system of care” that will ensure the timely and safe transfer and triage of acute patients to the centers, and the second is the management of these patients in the hospital stay during the acute period. In-hospital acute stroke practice is a comprehensive process that begins in neurological intensive care or stroke units, and the results are directly affected by the level and quality of stroke nursing practice. Acute stroke nursing consists of, but not limited to, effective and safe application of stroke-specific treatments; management of blood pressure, blood sugar, swallowing, nutrition and hydration; patient's posture, mobilization, early physical therapy and rehabilitation plan; monitoring of consciousness and ______________________________________________________________________________________________________________________________

Address for Correspondence: Prof. Mehmet Akif Topcuoglu MD, Hacettepe University Faculty of Medicine, Department of Neurology, 06100, Sihhiye, Ankara, Turkey.

Phone:+90 312 305 18 06 E-mail: matopcuoglu@yahoo.com

ORCID IDs: Mehmet Akif Topcuoglu 0000-0002-7267-1431, Zeliha Tulek 0000-0001-8186-6698, Sakine Boyraz 0000-0001-9699-6495, Atilla Ozcan Ozdemir 0000-0002-9864-6904, Aylin Ozakgul 0000-0001-9930-7739, Ayse Guler 0000-0003-4465-3743, Bijen Nazliel 0000-0002-6148-3814, Canan Togay Isikay 0000-0001-6256-9487, Erdem Yaka 0000-0002-6644-4240, Ethem Murat Arsava 0000-0002-6527-4139, Gulsen Caglar 0000-0002-8350- 1227, Hadiye Sirin 0000-0003-0262-3706, Ipek Midi 0000-0002-5125-3708, Murat Mert Atmaca 0000-0003-2048-4930, Naile Alankaya 0000-0002-3950- 2409, Nedim Ongun 0000-0003-1694-5933, Nurdan Yıldırım 0000-0002-9958-1786, Ozlem Aykac 0000-0003-4987-0050, Ozlem Kuçukguclu 0000-0002- 4771-1091, Oznur Usta Yesilbalkan 0000-0001-5607-0751, Recep Baydemir 0000-0001-9753-8461, Serefnur Ozturk 0000-0001-8986-155X, Turkan Acar 0000-0003-2001-914X, Mukadder Mollaoglu 0000-0002-9264-3059, Ayfer Karadakovan 0000-0002-7225-6810, Zehra Durna 0000-0001-8515-491.

This article should be cited as following: Topcuoglu MA, Tulek Z, Boyraz S, Ozdemir AO, Ozakgul A, Guler A, Nazliel B, Togay Isikay C, Yaka E, Arsava EM, Caglar G, Sirin H, Midi I, Atmaca MM, Alankaya N, Ongun N, Yildirim N, Aykac O, Kuçukguclu O, Usta Yesilbalkan O, Baydemir R, Ozturk S, Acar T, Mollaoglu M, Karadakovan A, Durna Z. Acute stroke nursing: standards and practical applications Turkish Cerebrovascular Disease Society and The Society of Neurologıcal Nursing Joint Strategy Project. Turkish Journal of Cerebrovascular Diseases 2020; 26(1): 1-96. doi: 10.5505/tbdhd.2020.41713

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neurological examination; venous thromboembolism, gastric ulcer and infection prophylaxis; prevention of complications such as KIBAS, infection, respiratory failure and bleeding and intensive care unit management and very effective patient, patient relative and team interaction and communication. This manuscript presents the fundamental practices and metrics adapted for our country from many current guidelines of acute stroke nursing.

Keywords: Stroke nursing, thrombolysis, thrombectomy, stroke unit, complication, quality, metric.

İNME HEMŞİRELİĞİ: STANDARTLAR VE PRATİK UYGULAMALAR KILAVUZU*

TÜRK BEYİN DAMAR HASTALIKLARI DERNEĞİ VE NÖROLOJİ HEMŞİRELİĞİ DERNEĞİ ORTAK STRATEJİ PROJESİ ÖZ

Akut inme klinik pratiğinde intravenöz tromboliz ya da trombektomi / aspirasyon gibi nörogirişimsel tedavilerin başarıyı yakalayabilmesi için iki uygulama ile desteklenmesi gerekir. Bunların ilki akut hastaların merkezlere zamanında ve güvenli triyajını sağlayacak olan “akut inme sevk ve idare sistemi”, diğeri ise bu hastaların akut dönem hastane kalışındaki uygulamalarıdır. Hastane uygulamaları nöroloji yoğun bakım veya inme ünitelerinde başlayan bir süreç olup sonuçları hemşirelik uygulamalarının kalitesinden doğrudan etkilenir. Akut inme hemşireliği inme spesifik tedavilerin etkin ve güvenli uygulaması, kan basıncı, kan şekeri, yutma, nütrisyon ve hidrasyonun yönetimi; hastanın postür, mobilizasyon, erken dönem fizik tedavi ve rehabilitasyon planı; bilinç ve nörolojik muayenenin takibi; ayrıca venöz tromboembolizm, gastrik ve enfeksiyon proflaksisi; KIBAS, enfeksiyon, solunumsal yetmezlik ve kanama gibi komplikasyonların önlenmesi ile yoğun bakımda hasta takibi ve çok etkili hasta, hasta yakını ve takım etkileşimi ve iletişimini içerir. Bu derleme akut inme hemşireliğinin birçok güncel rehberinin ülkemiz için adapte edilmiş temel uygulama ve metriklerini sunar.

Anahtar Sözcükler: İnme hemşireliği, tromboliz, trombektomi, inme ünitesi, komplikasyon, kalite, metrik.

*Authors of Subchapter

1. Stroke: a short review. 1.1. The epidemiology, importance, and the global burden of stroke, and future strategies (Serefnur Oztürk); 1.2.

Current standards for the treatment of acute ischemic stroke: Intravenous thrombolysis and thrombectomy (Recep Baydemir); 1.3.

Current treatments for acute intracerebral hemorrhage (Turkan Acar); 1.4. Acute stroke management systems: Stroke units and stroke centers (Ayse Guler, Hadiye Sirin)

2. Treatment and care for acute stroke. 2.1. Intravenous thrombolytic therapy for hyperacute ischemic stroke: Final checks before tPA administration, Preparation and administration of the medicine (Sakine Boyraz); 2.2. The first 24 hours after IV tPA: Monitoring of the patient, blood pressure monitoring, neurological examination follow-up, NIH stroke scale, and potentially common complications, bleeding, and orolingual edema (Sakine Boyraz); 2.3. Nursing management for neurointerventional procedures for the treatment of the acute stroke patient: Basic principles of patient follow-up after angiography and the treatment of major complications (Sakine Boyraz);

2.4. Perioperative and intraoperative neurology nursing in neurointerventional vascular procedures (Ozcan Ozdemir, Ozlem Aykac); 2.5.

Posture, mobilization, and early-stage physical therapy and rehabilitation in the acute ischemic stroke patient (Ayfer Karadakovan); 2.6.

Nursing practice in the hyperacute period of intracerebral hemorrhages and subarachnoid hemorrhages: Follow-up of the posture, blood pressure, neurological examination, and consciousness (Ayfer Karadakovan); 2.7. Major problems and nursing practices in patient follow- up after subarachnoid hemorrhage (Ipek Midi); 2.8. Neurological deterioration in an acute stroke patient: Follow-up, frequently encountered conditions, and treatments (Mukadder Mollaoglu); 2.9. Medical treatment and nursing approaches in brain edema and increased intracranial pressure in ischemic and hemorrhagic stroke (Ethem Murat Arsava); 2.10. Postoperative patient follow-up in the neurology intensive care unit (care after decompressive craniectomy, aneurysm surgery, and hematoma surgery) (Bijen Nazliel); 2.11.

Intra-hospital transfer of acute neurological patients (Mukadder Mollaoglu)

3. General provision of care and management of systemic problems. 3.1. Management of fever and the body temperature in the stroke patient (Mukadder Mollaoglu); 3.2. Oxygen therapy in the acute stroke patient (Erdem Yaka); 3.3. Evaluation of the swallowing function in the stroke patient (Murat Mert Atmaca); 3.4. Hydration and nutrition in the stroke patient: Evaluation, starting oral / non-oral feeding, monitoring, and calorie and protein supplements (Nedim Ongun); Nursing practices (Zeliha Tülek); 3.5. Follow up of blood glucose levels in the stroke patient (ZelihaTulek); 3.6. Oral care, airway management, oxygen therapy, and pneumonia prevention and treatment in the stroke patient (Gulsen Caglar); 3.7. DVT/PTE prophylaxis in the stroke patient (Gulsen Caglar); 3.8. Pressure ulcer in the stroke patient:

Risk, prevention, and treatment (Aylin Ozakgul); 3.9. Urinary incontinence, urinary catheters, prevention of urinary infections (Zeliha Tulek and Aylin Ozakgul)

4. Restorative nursing care for stroke patients in the long-term. 4.1. Communication with the stroke patient: Speech disorders (Ozlem Kuçukguclu); 4.2. Management of severely affected and minimally responsive stroke patients in the subacute period (Oznur Usta Yesilbalkan); 4.3. Physical disability, disability improvement, and rehabilitation in the stroke patient (Naile Alankaya); 4.4. Psychiatric and cognitive problems after a stroke (Ozlem Kuçukguclu)

5. After a stroke. 5.1. Planning the hospital discharge for an acute stroke patient, supportive care at home, palliative care (Zehra Durna, Nurdan Yildirim); 5.2. Nurse's role in the management of vascular risk factors in the stroke patient after the hospital discharge (Canan Togay Isikay)

6. Training to become a stroke nurse. 6.1. Education and training to become a stroke nurse: Needs, procedure, certification (Zehra Durna) Turkish Journal of Cerebrovascular Diseases 2020; 26(1): 1-96

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3 1. STROKE: A SHORT REVIEW

1.1. The epidemiology, importance, and the global burden of stroke, and future strategies

The term "cardiovascular diseases" includes coronary heart diseases, cerebrovascular diseases, hypertension, peripheral artery disease, rheumatic heart diseases, congenital heart diseases, heart failure, and cardiomyopathies.

The cerebrovascular disease category including stroke is the third most common disease group in the world. Today; seventeen million people have a stroke and six million people lose their lives from this disease every year. Based on statistical data reported from the United States, stroke holds the rank as a cause of death after heart diseases among all types of cardiovascular diseases. The prevalence of stroke has been reported as 2.7 percent in America. The prevalence of stroke increases with age in both sexes. Every year in the United States, 795,000 people have a stroke either for the first time in their lives (610,000 people) or as a recurrent stroke (185,000 people). Of all strokes, 87 percent are ischemic and 10 percent are hemorrhagic strokes. The remaining 3 percent are subarachnoid hemorrhages. One individual has a stroke every 40 seconds. The risk of lifelong stroke will decrease eliminating cardiovascular risk factors (1).

The projections made by the European Stroke Organisation (ESO) demonstrate that these observations will remain unchanged or aggravate.

It is forecasted that the proportion of old individuals in Europe will increase by 35 percent by the year 2050. Based on this forecast, the economic burden of cardiovascular disease is estimated to reach 1.1 trillion US Dollars. It is predicted that the prevalence of stroke will increase to 3.8 percent by 2030. The preventable curable nature of stroke offers an important opportunity for health authorities to reduce the burden of stroke. In its stroke action plan, ESO aimed a decline in stroke rates by 10 percent in 2030 and described strategic objectives accordingly (2).

The aging population in our country and changing lifestyle patterns have resulted in an increase in the rates of chronic diseases. The Turkish Statistical Institute (TUIK) reports that 35,000-40,000 people died of a stroke in the years 2015-2017 despite all efforts.

Every acute stroke patient needs multidisciplinary care delivered by specialists in a stroke unit; however, some patients need further interventions with advanced technological methods. Current literature indicates the utility of stroke units and stroke centers for this purpose.

These centers are designed to be equipped with adequate infrastructure, experienced personnel, and standard procedures to treat the majority of stroke patients (3). Studies demonstrate that more favorable outcomes are achieved in ischemic stroke patients treated in well-equipped centers with higher endovascular treatment rates with intravenous (IV) recombinant tissue plasminogen activators (rtPA) compared to those treated in public hospitals with no specific stroke units.

Developed as a consequence of years of work; the directive on the provision of health services for acute stroke patients paved the way to establish an effectively operating organization and a patient referral chain, achieving a major step for the treatment and transport of such patients to stroke units and stroke centers managed by neurologists (4). It is aimed to increase the number of the stroke units and centers rapidly, aiming to have at least 90% of stroke patients treated in such stroke units and centers in the year 2030 in line with the ESO targets. It is critical for the stroke units and centers to have experienced and competent healthcare professionals on board; as well as to be equipped with adequate infrastructure and technical instruments to treat and manage stroke patients (5). Another major contributor to the increased treatment success and improved quality of life of patients is to have experienced and competent nurses in the stroke team.

1.2. Current standards for the treatment of acute ischemic stroke: Intravenous thrombolysis and thrombectomy

Acute ischemic stroke is still the leading cause of disability in the world. However, the incidence of acute ischemic stroke is decreasing gradually owing to the innovative treatment methods developed over the last two decades. An ischemic stroke due to untreated large vessel obstruction causes two million nerve cells to lose function every minute. This is an important piece of information to understand the concept of 'time is brain' and the standards of treatment.

Recanalization and reperfusion are the main

Turkish Journal of Cerebrovascular Diseases 2020; 26(1): 1-96

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4 targets of acute stroke treatment. Achieving these targets result in a reduced area of infarction and may reverse neurological deficits. The treatment of acute ischemic stroke has evolved over the last three decades. The introduction of the intravenous (iv) thrombolysis was followed by mechanical thrombectomy with proven efficacy. Currently, stroke is a treatable disease with the use of iv thrombolysis and mechanical thrombectomy either alone or in combination. However, the time- dependent attributes of these treatments should not be overlooked.

The NINDS (National Institute of Neurological Disorders and Stroke) study about the use of alteplase; a tissue plasminogen activator (tPA) was published in 1995, starting a new period in acute ischemic stroke treatment (6). That randomized- controlled study demonstrated the 90-day favorable efficacy of tPA on daily functional outcomes (7). The following efficacy results from the ECASS-III (European Cooperative Acute Stroke Study-3) study were favorable too, allowing for a wider time window of 3-4.5 hours to apply iv tPA.

This study investigated standard doses of iv tPA use, reporting good functional outcomes in 418 patients [modified Rankin Scores (mRS) of 0-1 in 52.4% vs 45.2%; Odds ratio: 1.34; 95% Confidence Interval (CI): 1.01-1.76] despite a slight increase in hemorrhage rates (symptomatic intracerebral hemorrhage rates: 2.4% in the tPA group and 0.2%

in the placebo group). The mortality rate was not different (7.7% vs 8.4%) (8).

An analysis of data from 2775 patients;

pooled by including the participants of the NINDS rtPA study and other patients from other randomized studies, demonstrated that the efficacy increases parallel to the earlier start of the treatment. The treatment was observed to be most efficacious in patients; who received the medication in the first 90 minutes of the event. It was also observed that the administration of the treatment was useful until the 6th hour of the event although the benefits of the treatment were alleviated by time (9). To achieve a cure (full remission on the 90th day of the event) in a patient; it requires to treat 4.5 patients within the first 1.5 hours, 9 patients within the 1.5-3 hours, and 14 patients within the 3-4.5 hours of the event (10).

tPA is a serine protease in the endothelial membrane. It is normally synthesized by the endothelial cells. tPA catalyzes the conversion of

plasminogen to plasmin. Plasmin degrades fibrin, displaying a fibrinolytic or thrombolytic effect in the vessels. Furthermore, a tissue phase of the tPA- plasmin system exists. Since tPA shows 1000 times or more affinity for fibrin-dependent plasminogen, it has “fibrin selective” and “local thrombolytic”

effects; for example, different from urokinase.

Obtained by recombinant DNA technology, the tPA is used systemically in the treatment of many acute thrombotic/thromboembolic events. Of the calculated dose, 10% was administered as bolus and the rest is administered during one hour of infusion. Informed consent should be obtained from patients to be treated with iv tPA similar to obtaining informed consent before surgical treatment. Naturally; the patient has the right to refuse treatment, analogous to vital surgery.

However, one should make sure that the patient understands what he or she refuses (11). The use of iv rtPA for the treatment of acute ischemic stroke was licensed in 2006 in Turkey (12).

Symptomatic intracerebral hemorrhage is the most feared complication of such treatment.

Symptomatic intracerebral hemorrhage refers to a hemorrhagic transformation developing within the first 36 hours of the event, resulting in neurologic injury. A score of 4 or higher in the NIHSS (National Institutes of Health Stroke Scale) indicates neurological deficits. It is relieving that many later studies found hemorrhage rates lower than the 6.4% rate reported in the NINDS rtPA study. The fewer the protocol deviations, the lower is the risk of hemorrhage (11,13,14).

A neurologist should spend every effort to treat an acute ischemic stroke patient with intravenous thrombolytic therapy. Intravenous thrombolytic therapy is performed in centers;

where 24-hour working neurologist teams, brain tomography, laboratory facilities, and inpatient services are available. Also, these centers should have intensive care facilities meeting the standards. An ideal organization setup should address planning for hospital operations, establishing stroke units, liaising with emergency physicians, and building stroke teams (12,15).

Severe disability resulting from acute ischemic stroke occurs at a rate of 20-25%

associated with major cerebral artery stenoses.

Partial recanalization is observed with iv thrombolysis in acute stroke patients with occlusions of major cerebral arteries.

Recanalization is observed in the middle cerebral

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5 artery and basilar artery at rates of 30% and it is observed in the internal carotid artery at a rate of 10% (16).

Therefore, modes of invasive endovascular therapy have been a major subject of debate over the past 15 years. Interventional treatment with the use of old-generation devices and techniques for acute ischemic stroke treatment was found not superior to intravenous thrombolysis (17,18).

Furthermore, recent studies; employing new- generation technology and devices (stent- retrievers, balloon guide catheters, etc.) and improved organizational capacity for patient transport (short time elapsing from the time of symptom emergence until the angiography), have revealed the benefits of endovascular therapy (19- 23). Current modes of endovascular treatments allow for obtaining high recanalization and survival rates along with low rates of complications.

The results of multicenter randomized trials were reported in the period between November 2014 and April 2015, demonstrating the effectiveness of endovascular treatment. MR CLEAN (19), ESCAPE (21), EXTEND-IA (20), SWIFT PRIME (23), and REVAS-CAT (22) studies demonstrated the superiority of endovascular therapy over iv tPA therapy when either of these treatments was used alone in acute ischemic stroke patients due to acutely disrupted anterior cerebral circulation (24).

A cure is accepted as a one-point reduction in the Rankin score of the study patients and it is reported that only 2.6 patients needed neurothrombectomy based on a meta-analysis of the 5 abovementioned studies performed by the HERMES group (25,26).

The consistent results obtained from numerous studies and diverse patient populations led to the class-I recommendation with A-level evidence in the American Heart Association (AHA) 2015 treatment guidelines, stating that endovascular treatment with stent-retrievers was recommended for patients meeting described criteria (27).

The major factor acting on the treatment success of the endovascular treatment is the elapsing time. The immediate removal of the clot and the restoration of the blood perfusion at the affected area will improve the rates of functional recovery. Other components contributing to treatment success include the stroke severity and

the presence of penumbra; which is still the salvageable tissue detected with advanced imaging techniques. If penumbra is present, patients can benefit from treatment administered later than 6 hours of the event.

Based on these findings; a class-IA recommendation is made in the treatment guideline, recommending that current endovascular treatment techniques (thrombectomy with modern retrievable stents) can be applied within the 6 hours of the start of symptoms (from the time when the patient was last observed healthy or normal). After confirming the vascular occlusion with appropriate imaging studies (computed tomography and computed tomography angiography), patients; who were started intravenous thrombolytic therapy should be taken directly to the angiography unit without waiting for any response to the tPA therapy.

Patients; for whom tPA therapy is contraindicated, should be taken directly to the angiography unit after the imaging studies so that the endovascular interventions could be started (28).

The success of the stroke treatment depends on the transport of the patient to a stroke unit swiftly, the early utilization of multimodal imaging methods, and the immediate start of the treatment.

All cases in the stroke spectrum; suffering from minor symptoms to major ones, can end in catastrophic outcomes. Therefore, treatment should start immediately. Planning, organization, collaboration, and jobshare will all end in an increasing number of patients benefiting from treatment.

1.3. Current treatments for acute intracerebral hemorrhage

Intracerebral hemorrhage is a leading cause of mortality and morbidity in the world. Although clinical trials and treatment guidelines about intracerebral hemorrhage appear to lag behind those performed and developed for ischemic stroke and aneurysmal subarachnoid hemorrhage, studies in the fight against intracerebral hemorrhage have increased significantly over the past decade. Community-based studies demonstrate that survival with a minimal disability is possible for many patients (29,30).

Acute intracerebral hemorrhage cases can be subgrouped under two categories; which are hemorrhages of primary and secondary causes.

Primary causes include hypertension, cerebral

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6 amyloid angiopathy, anticoagulant/fibrinolytic use, antiplatelet use, drug dependency, and bleeding diatheses. Secondary causes include vascular malformations, aneurysms, tumors, hemorrhagic transformation of the cerebral infarct, and hemorrhages developing secondary to cerebral venous thrombosis (31).

Computed tomography (CT) and/or magnetic resonance imaging (MRI) should definitely be performed in patients with suspected intracerebral hemorrhage to make a differential diagnosis from ischemia. When necessary; CT- angiography, CT-venography, and CT-perfusion imaging can also be performed besides CT imaging. The most important prognostic factor in intracerebral hemorrhage is the volume of the hematoma. The volume of the hematoma increases particularly within the first four hours in the majority of the patients, causing clinical deterioration and unfavorable prognosis (32,33).

In cases of a hematoma in the posterior fossa or a hematoma with an extra-axial location, or in cortical subarachnoid hemorrhages; magnetic resonance imaging (MRI),fluid-attenuated inversion recovery(FLAIR),susceptibility-weighted imaging(SWI), and gradient echo sequences are useful to detect small hematomas in the acute stage when CT is not sufficient (34).

The treatment of intracerebral hemorrhage requires complex strategic planning as a combined procedure of patient management with hemostatic, surgical, and neuroprotective methods; as well as administering antihypertensive therapy (35). This patient management process is of prognostic importance;

especially when the patient is treated within the first 24 hours by an experienced team, favorably in a stroke unit if available or in a neurological intensive care unit. In patients with intracerebral bleeding; critical factors include airway and mechanical ventilation management, checking glucose levels, prevention and effective treatment of infection, maintenance of normothermia, meticulous fluid-electrolyte management, management of epileptic seizures, management of proper nutrition in the acute stage, prevention of deep vein thrombosis, gastrointestinal prophylaxis, and early mobilization of the patient (30,36-38).

It is recommended that elevations of intracranial pressure should be prevented and osmotic therapy with mannitol and hypertonic 3%

NaCl solution should be administered (39).

One of the major etiological factors in the etiology of intracerebral hemorrhage is elevated blood pressure; which should be controlled in the acute phase because it can increase the volume of the hematoma. Based on the INTERACT-2 study results, the current American Heart Association- American Stroke Association (AHA/ASA) guideline state that reducing the blood pressure to 140 mmHg or lower is safe and may improve functional outcomes (29). Treatment with esmolol, labetalol, nicardipine, sodium nitroprusside, nitroglycerin, or oral captopril can be administered (29,36).

In warfarin-induced bleeding cases; the administration of vitamin K, free frozen plasma, and more importantly prothrombin complex concentrates (PCC) contribute to both the normalization of INR values and the prevention of the expansion of the hematoma (35).

In intracerebral hemorrhage cases associated with standard heparin use, protamine sulfate (20 mg/min) should be administered as antidote therapy (40).

Studies continue to investigate potential agents to be used for the treatment of intracerebral hemorrhage due to factor Xa inhibitors Apixaban, Edoxaban, and Rivaroxaban, and due to Dabigatran; which is a direct thrombin inhibitor and a non–vitamin K antagonist oral anticoagulant (NOACs). The only approved treatment option today is Idarucizumab, which binds to Dabigatran reversing its effects. Studies continue, investigating the use of andexanet alfa for the treatment of Factor-Xa induced bleeding (41,42).

Evacuation of hematomas and decompression surgery is recommended for 3 cm or larger cerebellar hematomas based on some nonrandomized studies, which report favorable outcomes. External ventricular drainage can be performed for the treatment of intraventricular hematomas. Although benefits of decompressive surgery have not been established yet; it may reduce mortality, especially in patients with clinical deterioration and increased intracranial pressure (29,43).

In conclusion, there are many promising new developments in the treatment of intracerebral bleeding but mortality and morbidity rates remain to be critical. Therefore, the management of these patients by an experienced stroke team can

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7 prevent potential complications and contribute to a favorable prognosis.

1.4. Acute stroke management systems: Stroke units and stroke centers

Stroke is the second leading cause of death (44), and the third leading cause of permanent disability (45).However, the likelihood of recovery is high with early treatment. On the other hand, delays in starting the treatment curb the chances of recovery and contribute to elevated rates of disability.

The principles of acute stroke management have completely evolved after the demonstration of the efficacy of an iv tPA; which was administered in the first three hours of stroke onset (6). Randomized controlled studies investigating the efficacy of endovascular therapy in acute stroke and the reports about the clinical outcomes of those studies maintain the continuing evolution of acute stroke management. In the light of the growing number of clinical studies and accumulating clinical experience about acute stroke treatment, these patients started to be managed in stroke units with specially trained personnel, applying a multidisciplinary approach.

The most common causes of the decline in stroke- associated mortality observed over the last decades include the strategic management in stroke units and the organized approach in stroke treatment (46).

Many observational and controlled studies and metaanalyses demonstrated the favorable impact of stroke units on cases of acute ischemic stroke, hemorrhagic stroke, and transient ischemic attacks (TIAs) (47). The involvement of stroke units in the management of acute stroke cases is associated with 3-28 % reduction in specific mortality, 8-11% reduction in the length of hospital stay, and more importantly, 7-19%

increase of hospital discharge of disability-free patients compared to patient management in general inpatient units (47,48).

Certification studies of stroke units and of comprehensive stroke units licensed to administer invasive endovascular therapies are ongoing both in our country and the world to ensure the standardization of services and improve the quality.

Topçuoğlu et al. outlined the physical conditions, minimally required attributes of architecture and infrastructure of stroke units in

Turkey along with the basic requirements of staff competencies, basic therapeutic interventions, and standards of care in their article “Stroke Unit:

General principles and standards” published in 2015 in Turkish Journal of Cerebrovascular Diseases (47). The Directive on Health Services to be Provided to Acute Stroke Patients was issued on 18/07/2019 with the number 80118214 by the Republic of Turkey Ministry of Health, General Directorate of Health Services, Department of Health Services For Specialty Planning. The directive stipulated procedures and principles about the following issues; including the regulation of the provision of healthcare for the management of acute stroke patients; the organization of the manpower, medical equipment, physical conditions, and service criteria in the prospectively established stroke units; the development of the referral and transfer criteria for stroke patients; and the registration, inspection, and decertification of stroke units when necessary (4).

2. TREATMENT AND CARE FOR ACUTE STROKE 2.1. Intravenous thrombolytic therapy for hyperacute ischemic stroke

The iv administration of t-PA is the only approved pharmacological treatment by the Republic of Turkey Ministry of Health for the treatment of acute ischemic stroke. The treatment effects are time-bound. The administration of the treatment within 4.5 hours of the emergence of stroke symptoms or within 4.5 hours after the last normal observation of the patient affects clinical outcomes favorably. It is recommended that the time elapsed from the emergency service admission of the patient to the administration of treatment should not be longer than 60 minutes (11,49).

2.1.1. Final checks before tPA administration Blood-pressure should be effectively regulated. If systolic blood pressure (SBP) is <185 mmHg and diastolic blood pressure (DBP) is 110 mmHg in an acute ischemic stroke patient, IV tPA therapy can be applied. Extra interventions are not necessary in those cases; however, the patient should be followed-up closely. In patients with SBP values of 185-220 mmHg and DBP of 110-120 mmHg, the blood pressure values should be medically reduced to fall in the appropriate range before the iv administration of rt-PA. The algorithm for blood

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8 pressure management in patients to be treated with iv tPA has been adapted and published by the Cerebrovascular Diseases Working Group of the Turkish Neurological Society (50).

Two separate iv lines should be established for vascular access in those patients.

Consent forms should be obtained. Sample consent forms are provided on the website of Turkish Neurological Society and supplementally in the "Pocket Guide to Intravenous Tissue Plasminogen Activator Use For the Treatment of Acute Stroke" published by the Society (50).

Blood samples should have been collected.

The laboratory tests should include the assessments of basic biochemistry parameters, complete blood count, blood groups, aPTT, and INR. However, bedside measurement of INR levels in patients receiving warfarin and bedside measurements of blood glucose levels is sufficient.

ECG tracings and lung X-rays should be obtained but these tests should not cause a delay to start iv tPA.

The National Institutes of Health Stroke Scale (NIHSS) should have been scored. The exclusion criteria for starting iv tPA therapy should be checked. These criteria are summarized in Table I.

The "Pocket Guide to Intravenous Tissue Plasminogen Activator Use For the Treatment of Acute Stroke" published by the Society and other relevant guidelines developed by the society can be used as references (11,49,50).

If semi-invasive interventions such as urinary catheterization or insertion of a nasogastric catheter are necessary, it is recommended that they should be performed before tPA administration. Also, these procedures should not cause a delay to start iv tPA.

Table I. Absolute exclusion criteria for iv tPA administration in acute ischemic stroke.

IV rt-PA therapy is not administered

• If the treatment cannot be started within 4.5 hours after the onset of symptoms

• Any type of acute (intracerebral, subarachnoid, subdural) hemorrhage in imaging tests

• A demarcated and wide hypodense area in CT

• Systolic blood pressure >185 mmHg or diastolic blood pressure >110 mmHg

• Thrombocytopenia<100,000/mm3

• INR>1.7

• aPTT>40 seconds

2.1.2. Preparation and administration of the medicine

2.1.2.1. Points to consider before preparing thrombolytic therapy (Actilyse®)

- The lyophilized substance should be protected from light.

- It should be stored at temperatures lower than 25°C.

- The reconstituted solution can be stored in the refrigerator for up to 24 hours and can be stored in ambient temperatures of not higher than 25°C for up to 8 hours.

-Actilyse® solution for use should be reconstituted only with the sterile water provided in the original package of the medicine.

- No other fluids should be used.

- The solution should not be shaken at all (foaming should be avoided).

Each dose calculation should be checked twice. (Table II).

Any remaining medication surplus should be withdrawn from the vial of rt-PA and disposed of in medical waste containers.

- Actilyse® should always be administered through a separate iv line.

Table II. Dose table for iv rt-PA therapy.

Patient's weight Total dose Bolus dose Infusion dose

40 36 3,6 32,4

43 38,7 3,6 34,8

46 41,4 4,1 37,3

49 44,1 4,4 39,7

52 47,7 4,8 42,9

55 49,5 5,0 44,5

58 52,2 5,2 47

61 54,9 5,5 49,4

64 57,6 5,8 51,8

67 60,3 6,0 54,3

70 63 6,3 56,7

73 65,7 6,6 59,1

76 68,4 6,8 61,6

79 71,1 7,1 64

81 72,9 7,3 65,6

84 75,6 7,6 68

87 78,3 7,8 70,5

90 81 8,1 72,9

93 83,7 8,4 75,3

96 86,4 8,6 77,8

99 89,1 8,9 80,2

>100 90,0 9,0 81,0

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9 2.1.2.2. Preparing the tPA, infusion, and dosing

The tPA dose is 0.9 mg/kg for the treatment of acute stroke. The maximum dosage should not exceed 90 mg. Of the calculated dose, 10% was administered as a bolus and the rest is administered over a 60-minute infusion. While removing the bolus dose from the vial, air should not be injected into the vial. Using a 10 mL syringe, a 10% bolus dose is removed from the vial. For example, a 10% bolus dose corresponds to 6.8 mg or 6.8 ml for a total dose of 68 mg to be administered. The 10% bolus dose is infused over one minute. Care should be exercised during the reconstitution of the medicine. Phases of reconstituting the medicine are presented in detail in Figure I.

The patients should be monitored for hemorrhage and angioedema during and after an iv Actilyse® infusion.

During an iv Actilyse® infusion; the following should be monitored every 15 minutes for the first 2 hours: "blood pressure", "consciousness" (NIHSS items 1a, b, and c, Table III), and "motor deficits"

(NIHSS items 5 and 6, Table III).

If a new neurological disorder emerges or any clinical deterioration occurs during the iv Actilyse® application; the infusion should be stopped, the physician should be informed, and the patient should swiftly be transported for a CT scan.

After the Actilyse®infusion is completed, the iv line should be flushed with 3-5 ml of 0.9% NaCl.

Any use of acetylsalicylic acid or iv heparin should be avoided within the first 24 hours of Actilyse® therapy.

2.2. The first 24 hours after IV tPA: Monitoring of the patient, blood pressure monitoring, neurological examination follow-up, NIH stroke scale, and potentially common complications, bleeding, and orolingual edema 2.2.1. Patient monitorization

During an iv Actilyse® infusion; the patient should be monitored every 15 minutes for the following: blood pressure (Table IV), consciousness (NIHSS items 1a, b, and c, Table III), motor deficits (NIHSS items 5 and 6, Table III), major and minor bleeding, orolingual edema, and increased intracranial pressure (IICP). Any emergence of symptoms or suspicion requires urgent reporting to the physician. The rtPA infusion is stopped in those cases.

After completing the IV tPA infusion, the

patient should be followed up in the stroke unit or in the neurological intensive care unit for at least 24 hours.

After the iv rt-PA infusion is completed, the patient should be monitored "every 30 minutes"

for 6 hours and "every 60 minutes" for 16 hours for neurological changes (consciousness, pupillary light reaction, and motor deficits), major and minor bleeding symptoms, blood pressure, symptoms of increased intracranial pressure (IICP), and the symptoms of hypersensitivity and angioedema.

Before starting anticoagulant or antiplatelet therapy; as a standard practice, the physician should be consulted to obtain a control CT scan (or MRI) at the end of the 24 hours.

The patient should be monitored and necessary interventions should be performed for the potential complications of the iv rt-PA therapy;

as well as for the vital signs, blood glucose levels, and fluid resuscitation (Table V).

2.2.2. Blood pressure control

Invasive monitoring with arterial catheterization is not recommended unless absolutely necessary after the administration of iv tPA. Blood pressure is monitored noninvasively

“every 15 minutes” during the rt-PA administration and in the following 2 hours. Then, it should be monitored “every 30 minutes” for the next 6 hours and “every 60 minutes” for the next 16 hours.

Before the iv rt-PA administration, the blood pressure should be reduced to values less than 185/110 mmHg (Table IV). Also, the patients not receiving rt-PA therapy should be treated for blood pressure levels higher than 220/120 mmHg.

For blood pressure management before and after iv tPA therapy, the algorithm; which has been adapted for use in Turkey by the Cerebrovascular Diseases Working Group of the Turkish Neurological Society, is recommended to be used.

The algorithm can be found in the "Pocket Guide to Intravenous Tissue Plasminogen Activator Use For the Treatment of Acute Stroke"; which was developed by the Turkish Neurological Society (49,50). A short summary is provided in Table IV.

2.2.3. Neurological follow-up

The neurological status of the patient undergoing IV rt-PA therapy should be followed- up for 24 hours complying with standards of

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10 care. For this purpose; the pupillary light reflex, consciousness (NIHSS items 1 a, b, and c, Table V), motor deficits (NIHSS items 5 and 6, Table V), and epileptic seizures should be followed up routinely.

2.2.4. The National Institutes of Health Stroke Scale (NIHSS)

NIHSS is summarized in Table V. Basic principles should be followed to score NIHSS:

Scoring is always performed following the original order of ranking of the NIHSS items. No assistance is offered to the patient or no clues are provided.

The scores should always be attributed to the first attempts of the patient. Furthermore, only the actual performance of the patient should be scored. Consistency should always be maintained.

All types of deficits in the patient should be scored regardless of whether they are new or occurred previously (15,50,51).

2.2.5. tPA-associated hemorrhage

The most feared adverse effect of the iv rt-PA therapy is hemorrhage. Hemorrhage can be either a major or a minor bleeding. Major bleeding includes cerebral hemorrhage, retroperitoneal hemorrhage, gastrointestinal system (GIS) bleeding, and genitourinary system bleeding.

Minor bleeding includes gingival bleeding, nosebleed, hemoptysis, bleeding and ecchymoses at the site of iv intervention, and subcutaneous bleeding.

The most common type of major bleeding is intracerebral hemorrhage. The emergence of any sudden or unexpected elevations of the blood pressure, impaired consciousness, increased motor deficits, increased NIHSS scores, and a newly emerging headache or nausea and vomiting should suggest tPA-associated intracranial bleeding.

In these cases the tPA infusion is stopped.

The physician should be informed. Blood samples are immediately submitted to laboratory to test for complete blood count, INR, aPTT, and cross-match.

The patients is swiftly prepared for a CT scan and immediately transferred to the CT room as soon as the request is approved. Vigilance should be exercised for physician orders. To be ready for physician orders, the availability of cryoprecipitate and tranexamic acid are maintained. The orders for hematology and neurosurgery consultations

should be followed up. The blood pressure, IICP symptoms, -if possible - cerebral perfusion pressure, the mean arterial pressure, body temperature, and blood glucose levels should be followed up (50).

2.2.6. Management of orolingual edema

Infusion is stopped in patients; who developed orolingual edema. Orolingual edema is a common complication in patients taking angiotensin-converting enzyme inhibitors. In these cases, the physician should be informed immediately. The airway patency should be maintained. If the edema is limited to only the anterior part of the tongue and to the lips, endotracheal intubation may not be necessary.

However; the rapid spread of the edema to the larynx, the floor of the mouth, the palate, and the oropharynx may require endotracheal intubation.

The nurse should be ready for this intervention.

Because nasal intubation can cause epistaxis after an iv rt-PA infusion, the most appropriate method can be "awake fiberoptic intubation".

In these cases, iv rt-PA infusion is stopped and everything should be all set for the physician's orders. Probably; methylprednisolone 125 mg iv, diphenhydramine 50 mg iv will be ordered along with ranitidine 50 mg iv or famotidine 20 mg iv.

The physician may order a subcutaneous injection of 0.3 ml of 0.1% epinephrine or 0.5 ml nebulizer in cases with aggravating orolingual edema.

The patient should be followed up for dyspnea and anaphylaxis. rt-PA infusion can be continued under close monitoring of the patient if symptoms are very mild or stable. Everything should all be set for any interventions for anaphylaxis. If anaphylaxis occurs in a patient in the inpatient service, the patient should immediately be transferred to the neurological intensive care unit. If anaphylaxis symptoms emerge, everything should all be set up for the physician's orders. In summary, a 0.5-1 cc dose of adrenaline 1:1000 via intramuscular or subcutaneous injection to the vastus lateralis muscle is ordered. The adrenaline injection should not be administered intravenously. The dose can be repeated every 5 to 15 minutes depending on the patient's responses. A combination of parenteral antihistamine therapy and salbutamol 5 mg nebulizer is administered (11,50).

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Figure I. tPA preparation steps and details.

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Figure I cont. tPA preparation steps and details.